Automated lumen definition from 30 MHz intravascular ultrasound images

One prerequisite for standard clinical use of intravascular ultrasound imaging is rapid evaluation of the data. The main quantities to be extracted from the data are the size and the shape of the lumen. Until now, no accurate, robust and reproducible method to obtain the lumen boundaries from intravascular ultrasound images has been described. In this study, 21 different (semi-)automated binary-segmentation methods for determining the lumen are compared with manual segmentation to find an alternative for the laborious and subjective procedure of manual editing. After a preprocessing step in which the catheter area is filled with lumen-like grey values, all approaches consist of two steps: (i) smoothing the images with different filtering methods and (ii) extracting the lumen by an object definition method. The combination of different filtering methods and object definition methods results in a total of 21 methods and 80 experiments. The results are compared with a reference image, obtained from manual editing, by use of four different quality parameters—two based on squared distances and two based on Mahalanobis distances. The evaluation has been carried out on 15 images, of which seven are obtained before balloon dilation and eight after balloon dilation. While for the post-dilation images no definite conclusions can be drawn, an automated contour model applied to images smoothed with a large kernel appears to be a good alternative to manual contouring. For pre-dilation images a fully automated active contour model, initialized by thresholding, preceded by filtering with a small-scale median filter is the best alternative for manual delineation. The results of this method are even better than manual segmentation, i.e. they are consistently closer to the reference image than the average distance of all individual manual segmentations.     

MR renography: an algorithm for calculation and correction of cortical volume averaging in medullary renographs

We evaluated a mathematical algorithm for the generation of medullary signal from raw dynamic magnetic resonance (MR) data. Five healthy volunteers were studied. MR examination consisted of a run of 100 T1-weighted coronal scans (gradient echo; TR/TE 11/3.4 msec, flip angle 60 degrees; slice thickness 6 mm; temporal resolution 2 seconds). Gadolinium-diethylene triamine pentaacetic acid (DTPA; 0. 05 mmol/kg) was injected with an injector pump (5 ml/sec). Medullary MR renographs (MRRs) were calculated for regions of interest with strong and moderate cortical volume averaging (CVA). A reference medullary MRR, devoid of CVA, was obtained. Percentual signal differences between calculated and reference medullary MRRs were estimated for each consecutive scan. Run averaged values of these differences were calculated. Mean values, after subtraction of the resting state signal, were +0.2% (SD 9.7%) and +0.7% (SD 9.0%) for areas with strong and moderate CVA, respectively. We conclude that with this algorithm reliable extraction of medullary MRRs is feasible, providing a unique tool for clinical evaluation of medullary disease. J. Magn. Reson. Imaging 2000;12:453-459.     

Understanding Atypical Emotions Among Children with Autism

Children with autism are said to be poor mind readers: They have a limited understanding of the role that mental states play in determining emotions and behavior. In this research, 23 high-functioning children from the autistic spectrum (M age 9 years 3 months), 42 6-year-old controls, and 43 10-year-old controls were presented with six emotion-evoking stories and they were asked to explain protagonists' typical and atypical emotions. In the case of typical emotions, as expected on the basis of the mindblind hypothesis, children from the autistic spectrum gave few mental state explanations, referring to fewer than even the 6-year-old control group. However, in the case of atypical emotions, the autistic group performed as well as the 10-year-old controls. Their explanations for the atypical emotions demonstrate that children from the autistic spectrum indeed have the capacity to mind read (with respect to both desires and beliefs), although they do not always use this capacity in the same way as normally developing children. It is argued that the mind-reading capacity of high-functioning children from the autistic spectrum might be basically intact; unused in everyday circumstances but not necessarily defective.     

Serum triiodothyronine levels and inflammatory cytokine production capacity

Increasing evidence suggests that pro-inflammatory cytokines are at play in lowering peripheral thyroid hormone levels during critical illness. Conversely, thyroid hormones have been suggested to enhance production of inflammatory cytokines. In view of these considerations, we hypothesized a mutual association between triiodothyronine and pro-inflammatory cytokines. Therefore we evaluated the relation between both circulating and induced inflammatory markers and serum thyroid function parameters in the Leiden 85-plus Study. We found that higher circulating levels of inflammatory markers were associated with lower levels of free serum triiodothyronine. In turn, higher serum free triiodothyronine levels were related to higher production capacity of pro-inflammatory cytokines after stimulation with lipopolysaccharide. By combining in vivo and ex vivo data, we were able to demonstrate for the first time the existence of a potential feedback mechanism between thyroid function and immune production capacity. We conclude that maintenance of normal thyroid function might be important for a preserved immune response in elderly human populations.     

Vitamin D deficiency among HIV type 1-infected individuals in the Netherlands: effects of antiretroviral therapy

Vitamin D regulates bone metabolism but has also immunoregulatory properties. In HIV-infected patients bone disorders are increasingly observed. Furthermore, low 1,25(OH)(2)D(3) levels have been associated with low CD4(+) counts, immunological hyperactivity, and AIDS progression rates. Few studies have examined the vitamin D status in HIV-infected patients. This study will specifically focus on the effects of antiretroviral agents on vitamin D status. Furthermore, the effect of vitamin D status on CD4 cell recovery after initiation of HAART will be evaluated. Among 252 included patients the prevalence of vitamin D deficiency (<35 nmol/liter from April to September and <25 nmol/liter from October to March) was 29%. Female sex, younger age, dark skin, and NNRTI treatment were significant risk factors in univariate analysis, although in multivariate analyses skin pigmentation remained the only independent risk factor. Median 25(OH)D(3) levels were significantly lower in white NNRTI-treated patients [54.5(27.9-73.8) nmol/liter] compared to white PI-treated patients [77.3 (46.6-100.0) nmol/liter, p = 0.007], while among nonwhites no difference was observed. Both PI- and NNRTI-treated patients had significantly higher blood PTH levels than patients without treatment. Moreover, NNRTI treatment puts patients at risk of elevated PTH levels (>6.5 pmol/liter). Linear regression analysis showed that vitamin D status did not affect CD4 cell recovery after initiation of HAART. In conclusion, 29% of the HIV-1-infected patients had vitamin D deficiency, with skin color as an independent risk factor. NNRTI treatment may add more risk for vitamin D deficiency. Both PI- and NNRTI-treated patients showed higher PTH levels and might therefore be at risk of bone problems. Evaluation of 25(OH)D(3) and PTH levels, especially in NNRTI-treated and dark skinned HIV-1-infected patients, is necessary to detect and treat vitamin D deficiency early.     

New insights into the effects of biomaterial chemistry and topography on the morphology of kidney epithelial cells

Increasing incidence of renal pathology in the western world calls for innovative research for the development of cell‐based therapies such as a bioartificial kidney (BAK) device. To fulfil the multitude of kidney functions, the core component of the BAK is a living membrane consisting of a tight kidney cell monolayer with preserved functional organic ion transporters cultured on a polymeric membrane surface. This membrane, on one side, is in contact with blood and therefore should have excellent blood compatibility, whereas the other side should facilitate functional monolayer formation. This work investigated the effect of membrane chemistry and surface topography on kidney epithelial cells to improve the formation of a functional monolayer. To achieve this, microtopographies were fabricated with high resolution and reproducibility on polystyrene films and on polyethersulfone‐polyvinyl pyrrolidone (PES‐PVP) porous membranes. A conditionally immortalized proximal tubule epithelial cell line (ciPTEC) was cultured on both, and subsequently, the cell morphology and monolayer formation were assessed. Our results showed that L‐dopamine coating of the PES‐PVP was sufficient to support ciPTEC monolayer formation. The polystyrene topographies with large features were able to align the cells in various patterns without significantly disruption of monolayer formation; however, the PES‐PVP topographies with large features disrupted the monolayer. In contrast, the PES‐PVP membranes with small features and with large spacing supported well the ciPTEC monolayer formation. In addition, the topographical PES‐PVP membranes were compatible as a substrate membrane to measure organic cation transporter activity in Transwell® systems. Copyright © 2016 John Wiley & Sons, Ltd.     

Integrating mental health care into residential homes for the elderly: an analysis of six Dutch programs for older people with severe and persistent mental illness

Integrating mental health care into residential homes for the elderly is a potentially effective model to address the complex care needs of older chronically mentally ill people. Because no research was available on the implementation of such integrated care in practice, six programs already operating in the Netherlands were analyzed. At the administrative level, three types of cooperative arrangements existed: a psychiatric hospital renting a unit in a residential home for the elderly, a psychiatric hospital stationing mental health professionals in a residential home on a permanent basis, and a residential home employing its own psychiatrically trained staff. At the operational level, contrasting views emerged on the relation-ship between physical and mental health care; these were delivered separately or in integrated form. In either case, the employees trained as elder care workers or as psychiatric nurses had difficulties understanding each other because they held different ideas about good-quality care. These care visions can be characterized as the care-giving approach (care workers) versus the problem-oriented and the rehabilitation approaches (nurses). At the housing level, two models existed: mentally ill patients having apartments in a separate unit (concentrated housing) or located throughout the facility (dispersed housing). The most promising model appears to be the one in which a psychiatric hospital assigns mental health professionals to work in a residential home, where they remain administratively and operationally distinct from the standard residential services. Whether or not the psychiatric residents should be housed in separate units could not be decided based on this study.     

Variation and heritability of Hb F and F-cells among beta-thalassemia heterozygotes in Hong Kong

Enhanced fetal hemoglobin (Hb F) production can partially compensate for the lack of adult hemoglobin (Hb A) in patients with beta-thalassemia major or intermedia, and ameliorate the clinical severity of these diseases. To further elucidate factors governing Hb F levels, we evaluated demographic, clinical, laboratory, and genetic characteristics in 241 unrelated adult beta-thalassemia carriers in Hong Kong. They had wide variations in Hb F and F-cell numbers skewing toward higher levels. Individuals who coinherited the Xmn IT-allele in the (G)gamma-globin gene promoter had higher Hb F and more F-cells compared with those lacking the Xmn I T-allele. However, both groups exhibited a similarly wide spread of Hb F and F-cells. The correlation of Hb F and F-cells corresponded well to both linear and exponential models, suggesting multiple mechanisms for Hb F augmentation. The heritabilities of Hb F and F-cells were calculated in 66 families (111 parents who were beta-thalassemia carriers and 82 asymptomatic offspring) to be 0.7 to 0.9. The Xmn I polymorphism accounted for 9% of the Hb F and 13% of the F-cell heritabilities. These results suggest that these family members are well suited for genome wide association studies that will identify genetic loci regulating Hb F production, and likely novel pharmacological targets for reactivating Hb F production in adults.     

Cationic uremic toxins affect human renal proximal tubule cell functioning through interaction with the organic cation transporter

Several organic cations, such as guanidino compounds and polyamines, have been found to accumulate in plasma of patients with kidney failure due to inadequate renal clearance. Here, we studied the interaction of cationic uremic toxins with renal organic cation transport in a conditionally immortalized human proximal tubule epithelial cell line (ciPTEC). Transporter activity was measured and validated in cell suspensions by studying uptake of the fluorescent substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium-iodide (ASP⁺). Subsequently, the inhibitory potencies of the cationic uremic toxins, cadaverine, putrescine, spermine and spermidine (polyamines), acrolein (polyamine breakdown product), guanidine, and methylguanidine (guanidino compounds) were determined. Concentration-dependent inhibition of ASP⁺ uptake by TPA, cimetidine, quinidine, and metformin confirmed functional endogenous organic cation transporter 2 (OCT2) expression in ciPTEC. All uremic toxins tested inhibited ASP⁺ uptake, of which acrolein required the lowest concentration to provoke a half-maximal inhibition (IC₅₀?=?44?±?2 μM). A Dixon plot was constructed for acrolein using three independent inhibition curves with 10, 20, or 30 μM ASP⁺, which demonstrated competitive or mixed type of interaction (K _i?=?93 ± 16 μM). Exposing the cells to a mixture of cationic uremic toxins resulted in a more potent and biphasic inhibitory response curve, indicating complex interactions between the toxins and ASP⁺ uptake. In conclusion, ciPTEC proves a suitable model to study cationic xenobiotic interactions. Inhibition of cellular uptake transport was demonstrated for several uremic toxins, which might indicate a possible role in kidney disease progression during uremia.